Arachidonic acid is converted to a cascade of products which possess a high degree of biological activity. These metabolites of arachidonic acid include cyclooxygenase products such as primary bisenoic prostaglandins, prostacyclin and thromboxane as well as lipoxygenase products such as leukotrienes. Many studies on the hemodynamic influences of the primary prostaglandins have been carried out, however, none of these substances has been firmly established as a physiological mediator of blood flow regulation. Major goals of the proposed research project are to improve our understanding of the role of arachidonic acid and its biosynthetic products in the regulation of peripheral vascular resistance and distribution of blood flow in regional vascular beds. A major thrust of these studies will be to investigate vascular actions of thromboxane A2 and prostacyclin in in vivo animal models under conditions of altered biosynthetic capacity, e.g., ureter obstructed kidney. These studies will be carried out under conditions of both controlled and natural blood flow in the intestinal, renal and skeletal muscle vascular beds. Under conditions of controlled blood flow, changes in vascular resistance are directly reflected by changes in perfusion pressure. Noncannulating electromagnetic flow probes will be used to measure blood flow in peripheral regional beds under conditions of free flow and will provide information regarding the influence of these agents on regional beds under natural physiologic conditions. Formation and release of prostaglandins will be determined by RIA techniques. Interaction of arachidonic acid metabolites with vasoactive hormones sympathetic nerve stimulation and influences of inhibitors of arachidonic acid metabolism in the peripheral vascular bed will also be investigated. Overall knowledge gained from these studies should improve our understanding of the role of arachidonic acid and its metabolites in control of peripheral hemodynamics, and should provide insights into treatment of diseases such as essential hypertension.